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Effects of theophylline on radioiodide uptake in MCF-7 breast cancer and NIS gene-transduced SNU-C5 colon cancer cells.

Authors
Yoon, JK; Park, BN; Paik, JY; Jung, KH; Ko, BH; Lee, KH
Citation
Cancer biotherapy & radiopharmaceuticals, 24(2):201-208, 2009
Journal Title
Cancer biotherapy & radiopharmaceuticals
ISSN
1084-97851557-8852
Abstract
BACKGROUND: We investigated whether theophylline has the potential to increase radioiodide uptake in nonthyroidal cancer cells. MATERIALS AND METHODS: MCF-7 cells that express endogenous sodium/iodide symporter (NIS) and SNU-C5 cells adenovirally transduced with the human NIS gene (SNU-C5/NIS) were treated with 10(-7)-2x10(-4) mol/L theophylline for 24 hours before incubation with (125)I, and then, radioiodide uptake and retention were measured. NIS expression was assessed by immunohistochemistry and Western blot analysis, using an antihuman NIS monoclonal antibody. RESULTS: Theophylline at 10(-6)-2x10(-4) mol/L significantly and dose dependently augmented radioiodide uptake in MCF-7 cells and at 10(-6)-10(-5) mol/L in SNU-C5/NIS cells, without affecting radioiodide efflux. Abrogation by KClO(4)(-) demonstrated that the effect of theophylline occurred through specific iodide transport. Immunohistochemistry revealed dose-dependent increases of NIS staining in MCF-7 and SNU-C5/NIS cells by 10(-6)-10(-4) and 10(-6)-10(-5) mol/L theophylline, respectively. Western blot analysis demonstrated similar findings, showing increased expression of NIS on the membrane of SNU-C5/NIS and MCF-7 cells by theophylline treatment. CONCLUSIONS: Theophylline can augment radioiodide uptake in breast cancer cells and NIS gene-transduced cancer cells through the upregulation of NIS expression. Therefore, further investigations are warranted to explore the potential utility of this phenomenon for enhancing radioiodide-based imaging and therapies of NIS gene-transduced cancer cells.
MeSH terms
Biological TransportBreast Neoplasms/geneticsBreast Neoplasms/metabolism*Breast Neoplasms/therapyCell Line, TumorColonic Neoplasms/geneticsColonic Neoplasms/metabolism*Colonic Neoplasms/therapyGene TherapyHumansImmunohistochemistryIodine Radioisotopes/pharmacokinetics*Iodine Radioisotopes/therapeutic useSymporters/biosynthesis*Symporters/geneticsSymporters/metabolismTheophylline/pharmacology*Transduction, GeneticTransfectionTumor Cells, Cultured
DOI
10.1089/cbr.2008.0555
PMID
19409042
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Nuclear Medicine & Molecular Imaging
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